We have demonstrated that peripheral blood T (thymus-derived) lymphocytes from patients with untreated Hodgkin's disease show impaired in vitro function as judged by the inability to bind sheep erythrocytes to the cell surface (E-rosette formation), and an inability to increase protein synthesis after incubation with the plant lectin, phytohemagglutinin (PHA). The impaired function is reversible, since incubation of the T lymphocytes in tissue culture medium and fetal calf serum for several hours restores these in vitro responses to normal. In addition, we have demonstrated an apparently specific interaction between a serum factor and T lymphocytes from patients with Hodgkin's disease, which results in impaired T cell function. An immunosuppressive factor which may prove to be identical to the serum factor has also been extracted frm the spleen. Our goal is to extend these studies to determine (a) the nature and specificity of the serum factor in Hodgkin's disease, (b) the nature and specificity of the receptor on the T lymphocyte in Hodgkin's disease which binds this serum factor, (c) the mechanism by which the binding of the serum factor to the T cell surface receptor results in impaired T cell function, and (d) the pathogenesis of the altered T cell surface and serum constituents in Hodgkin's disease.